Recent work with probe molecules for the small pore system (hemepeptides) has led to the discovery of transendothelial channels formed by chains of fused plasmalemmal vesicles in the wall of muscle capillaries (rat diaphragm). Freeze cleaved preparations of reliably identified segments of the microvasculature (arterioles, capillaries, venules) have shown that there are characteristic segmental variations in the organization of cell junctions in the vascular endothelium. This and other findings suggest that the structural basis of permeability varies from segment to segment. It is proposed: 1) to check this assumption by studying the behavior of tracers in well identified segments of the microvasculature; 2) to obtain quantitative data on the net outflow of macromolecular tracers for each segment of the vasculature (by combining morphometry with the use of radioactive tracers; 3) to study local variations on endothelial surface chemistry using labeled lectins and vasoactive peptides; 4) to isolate capillary endothelia in sufficient amount for cell fractionation.